The candidate, Sean Berenholtz, is on the faculty at Johns Hopkins University, in the Division of Adult Critical Care Medicine (CCM), Department of Anesthesiology/CCM. His goal is to become an independent clinician scientist focused on applying rigorous research design to quality improvement in the intensive care unit, with an emphasis on evaluating alternatives to allogeneic blood transfusion in critically ill patients. To realize this goal, he will enroll in a formal advanced degree program in clinical investigation and he will receive structured mentoring by senior investigators for the conduct of supervised, innovative research. The specific aims and related hypothesis of the proposed research are: 1. To identify preoperative patient or hospital characteristics that predict allogeneic transfusion in adult patients undergoing spine surgery in Maryland from 1997 to 2000. We will analyze hospital discharge data for adult patients in non-federal acute care hospitals in Maryland who had a primary procedure code for spine surgery from 1997 to 2000 (n=3988). We hypothesize that preoperative patient characteristics, including advanced age and the presence of cardiac disease, are associated with an increased incidence of allogeneic transfusion. 2. To determine the association of allogeneic blood transfusion with clinical and economic outcomes following high-volume surgeries at Johns Hopkins Hospital. We will conduct a prospective review of data from the Johns Hopkins discharge database. We hypothesize that there is a dose-response association between anincreased number of allogeneic transfusions and an increased incidence of postoperative complications, including nosocomial infections, ICU length of stay, and hospital costs. 3. Assess the efficacy and safety of epsilon aminocaproic acid (EACA) in reducing allogeneic blood transfusion requirements in 170 patients undergoing spine surgery at Johns Hopkins Hospital. We will conduct a randomized controlled trial of EACA versus placebo in 170 patients undergoing spine surgery and we have completed a pilot study demonstrating the feasibility of this approach. We hypothesize that patients receiving EACA will require 30% fewer allogeneic blood transfusions than patients receiving placebo. 4. Evaluate the impact of EACA on economic outcomes, including hospital length of stay (LOS) and direct costs of hospital care in patients undergoing spine surgery at Johns Hopkins Hospital. We hypothesize that thedirect costs of EACA are less than those in the control group. Completion of the proposed research will significantly advance our knowledge of who is likely to require allogeneic transfusion, the complications associated with transfusion, and strategies to reduce transfusion exposure. These projects and the career development plan described will build a foundation for a successful career as an independent investigator.